Is CAPRIN1 p.Ile57Phe (c.169A>T) pathogenic?

CAPRIN1 p.Ile57Phe (c.169A>T) is classified Uncertain significance in CAPRIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-03). AlphaMissense: likely pathogenic (0.8168); Very rare (popmax 8.48e-05%, nfe).

How common is CAPRIN1 p.Ile57Phe (c.169A>T) in the general population?

CAPRIN1 p.Ile57Phe (c.169A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CAPRIN1 p.Ile57Phe (c.169A>T)?

AlphaMissense predicts likely pathogenic (score 0.8168) — an in-silico prediction, not a clinical call.

CAPRIN1 p.Ile57Phe

c.169A>T · rs1850347042 · VCV2475678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8168 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8168	likely pathogenic
REVEL	0.179	moderately benign-leaning
SaProt	LLR -12.19	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.1, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 173 bp · p 0.016 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,218 alleles

Overall 6.21e-05% 1/1,611,288 alleles · very rare exomes 1/1,459,142 · genomes 0/152,146 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CAPRIN1
Protein: p.Ile57Phe
Coding: c.169A>T
MANE Select: NM_005898
dbSNP: rs1850347042
Type: single nucleotide variant
Location: chr11:34052589 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 6 PDB

Full CAPRIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPRIN1 p.Ile57Thr Uncertain significance ★ ⚠ same residue
CAPRIN1 p.Arg458Ter Pathogenic ★★ same type
CAPRIN1 p.Arg132Cys Uncertain significance ★★ ⚠ same type
CAPRIN1 p.Gln206Arg Uncertain significance ★★ ⚠ same type
CAPRIN1 p.Pro424Leu Uncertain significance ★★ ⚠ same type
CAPRIN1 p.Pro528Thr Uncertain significance ★★ ⚠ same type
CAPRIN1 c.1122+19G>A Benign ★★ same type
CAPRIN1 c.217-5C>G Likely pathogenic ★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/caprin1-p-ile57phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown